This program is designed to identify primary chemical and structural alterations in DNA leading to neoplastic transformation in human cells and rodent cells and quantitate the repair response of the cells to agents which induce the primary alterations. The immediate objectives are to develop methods to transform human epithelial cells and to compare the type of lesions caused by low level (nontoxic) insults to DNA with high level (toxic) insults and measure the cell repair response to these lesions. The lesions currently of most interest are DNA-protein crosslinks, including both their induction and repair.